钙敏感受体参与黄芪甲苷减轻脑缺血再灌注损伤的保护作用  

Calcium-sensing receptor participate in protective effect of AstragalosideⅣon alleviating cerebral ischemia-reperfusion injury

作　　者：杜澍金[1] 赵艳萌 靳晓飞 高维娟[1] DU Shu-jin;ZHAO Yan-meng;JIN Xiao-fei;GAO Wei-juan(Hebei Key Laboratory of Chinese Medicine Research on Cardio-cerebrovascular Disease,Hebei University of Chinese Medicine,Shijiazhuang 050200,China)

机构地区：[1]河北中医学院,河北省心脑血管病中医药防治研究重点实验室,石家庄050200

出　　处：《中华中医药杂志》2020年第5期2506-2510,共5页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：河北省自然科学基金面上项目(No.H2019423074);河北省2019年研究生创新资助项目(No.CXZZBS2019156);河北中医学院科技能力提升项目(No.KTY2019049);河北中医学院优秀青年教师基础研究计划项目(No.YQ2019007)。

摘　　要：目的:探讨钙敏感受体(CaSR)参与黄芪甲苷减轻脑缺血再灌注损伤(CIRI)的作用。方法:以线栓堵塞大脑中动脉/再灌注建立大鼠CIRI模型,缺血2h后再灌注24h,分为假手术组、模型组、黄芪甲苷组、钙敏感受体激动剂+黄芪甲苷组。TTC染色观察脑梗死体积;HE染色观察脑组织病理形态变化;TUNEL染色法观察细胞凋亡情况;Western blot测定CaSR和Caspase-3蛋白表达水平。结果:与模型组比较,黄芪甲苷组可缩小脑梗死面积,减轻脑组织病理损害,减少细胞凋亡,降低CaSR表达量,抑制Caspase-3表达(P<0.05)。与黄芪甲苷组比较,钙敏感受体激动剂+黄芪甲苷组脑梗死面积增大,脑组织病理损害加重,细胞凋亡增多,CaSR及Caspase-3表达增多(P<0.05),黄芪甲苷减轻CIRI的保护作用被CaSR激动剂GdCl3大部分抑制。结论:黄芪甲苷可减轻CIRI,其机制可能与下调CaSR表达、抑制细胞凋亡有关。Objective:To investigate the role of calcium-sensing receptor(CaSR)in the protective effect of AstragalosideⅣ(AST-Ⅳ)in alleviating cerebral ischemia-reperfusion injury(CIRI).Methods:A rat model of focal CIRI was induced by occlusion of the left middle cerebral artery for 2h using the with thread plug,and then remove the plug to restore blood reperfusion(MCAO/R).Rats were randomly divided into control group(Sham),cerebral ischemia-reperfusion injury group(MCAO/R),the AST-Ⅳ,Calcium sensitive receptor agonist group(GdCl3+AST-Ⅳ).The volume of cerebral infarction was observed by TTC staining.HE staining was used to observe the pathological changes of brain tissue.TUNEL staining was used to evaluate apoptosis of nerve cells.The protein expressions of CaSR and Caspase-3 were detected by Western blot.Results:Compared with MCAO/R group,AST-Ⅳcould reduce the cerebral infarct volume of MCAO/R rats,improve the pathological damage of brain tissue,reduce cell apoptosis,inhibit the protein expression of CaSR and Caspase-3(P<0.05).Compared with the AST-Ⅳgroup,the cerebral infarct volume,the protein expression of CaSR and Caspase-3,and apoptotic cells increased,the pathological damage of brain tissue aggravated(P<0.05),the protective effect of AST-Ⅳin alleviating cerebral ischemia-reperfusion injury could be largely inhibited by CaSR agonists(GdCl3).Conclusion:AST-Ⅳmay have a protective effect on reducing CIRI.Its mechanism may be related to down-regulating of CaSR and inhibiting apoptosis.

关 键 词：黄芪甲苷 脑缺血再灌注损伤 钙敏感受体 细胞凋亡 机制 

分 类 号：R285.5[医药卫生—中药学]